The overarching aim of the current application is to examine whether a 12-hour nicotine withdrawal period (versus no withdrawal) among daily smokers results in greater fearful responding to induced bodily sensations among those with Panic Disorder (PD), as compared to those without PD. Specifically, we will examine whether smokers with PD compared to those without PD experience increased fearful responding to, and delayed recovery from, a 10% carbon dioxide-enriched air (CO2) laboratory procedure, as measured by: (1) post-challenge level of anxiety focused on bodily sensations and intensity of panic attack symptoms;(2) change in expired pCO2 from pre- to post-challenge;and (3) rate of recovery from the challenge in terms of anxiety focused on bodily sensations and expired pCO2. PUBLIC HEALTH RELEVANCE: The results of the study will directly inform smoking-panic comorbidity models, and serve more generally as an illustration of how unhealthy behaviors (smoking) affect and maintain mental health impairment. Overall, the proposed investigation represents a clinically significant test for a program of research aimed at understanding the mechanisms underlying highly prevalent panic-smoking comorbidity problems, which ultimately will inform the development of novel specialized interventions, with the goal of improving mental and physical health simultaneously via smoking cessation efforts that specifically address issues of such comorbidity among this difficult-to-treat population.